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The results demonstrate the feasibility of using rBA.5 ZsG-Nluc to track viral infections and identify prophylactics and therapeutics against recent SARS-CoV-2 VoCs in vitro, ex vivo, and in vivo.
This work indicates that SARS-CoV-2 can tolerate substantial impairment of proofreading but only when residual exonuclease activity remains above a minimal threshold, and defines this activity threshold to help guide antiviral strategies that target coronavirus proofreading.
The synergistic relationship between nsp15 and ORF6 is essential for efficient SARS-CoV-2 replication and it is hypothesized that since nsp15 functions by reducing dsRNA upstream of ORF6, nsp15 acts as a more potent antagonist leaving little activity for ORF6 to account for.
The reduced pathogenicity of rSARS-CoV-2 Nsp1 mutants highlights the potential for targeting Nsp1 for rational design of viral inhibitors and development of live-attenuated vaccine strategies as effective prophylactic and therapeutic treatments to combat SARS-CoV-2 and possibly other CoV infections.
Using the ferret model of influenza infection and transmission, it is demonstrated that the currently circulating B3.3.13 is already well adapted for mammalian infection and transmission whereas D1.1 rapidly acquires mammalian-adaptive mutations after a single infection and/or transmission event, highlighting its evolu...
A genome engineering technology is used to change a single amino acid in the viruses’ main protease enzyme to match that of circulating Omicron isolates to demonstrate antiviral efficacy of approved drugs and uncover mutants with reduced drug sensitivity.
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